PDBsum entry 4xcl

Chaperone

PDB id: 4xcl

Contents

Protein chain

214 a.a.

Ligands

AGS

Metals

_MG

Waters ×288

PDB id:

4xcl

Name:

Chaperone

Title:

N-terminal domain of hsp90 from dictyostelium discoideum in complex with ags

Structure:

Heat shock cognate 90 kda protein. Chain: a. Fragment: n-terminal domain, unp residues 1-223. Synonym: heat shock protein 90. Engineered: yes

Source:

Dictyostelium discoideum. Slime mold. Organism_taxid: 44689. Strain: ax2. Gene: hspd. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.21Å R-factor: 0.160 R-free: 0.181

Authors:

S.Raman,K.Suguna

Key ref:

S.Raman et al. (2015). First Structural View of a Peptide Interacting with the Nucleotide Binding Domain of Heat Shock Protein 90. Sci Rep, 5, 17015. PubMed id: 26599366 DOI: 10.1038/srep17015

Date:

18-Dec-14 Release date: 09-Dec-15

Protein chain

P54651  (HSC90_DICDI) -  Heat shock cognate 90 kDa protein from Dictyostelium discoideum

Seq: 700 a.a.

Struc: 214 a.a.

DOI no: 10.1038/srep17015

Sci Rep 5:17015 (2015)

PubMed id: 26599366

First Structural View of a Peptide Interacting with the Nucleotide Binding Domain of Heat Shock Protein 90.

S.Raman, M.Singh, U.Tatu, K.Suguna.

ABSTRACT

The involvement of Hsp90 in progression of diseases like cancer, neurological disorders and several pathogen related conditions is well established. Hsp90, therefore, has emerged as an attractive drug target for many of these diseases. Several small molecule inhibitors of Hsp90, such as geldanamycin derivatives, that display antitumor activity, have been developed and are under clinical trials. However, none of these tested inhibitors or drugs are peptide-based compounds. Here we report the first crystal structure of a peptide bound at the ATP binding site of the N-terminal domain of Hsp90. The peptide makes several specific interactions with the binding site residues, which are comparable to those made by the nucleotide and geldanamycin. A modified peptide was designed based on these interactions. Inhibition of ATPase activity of Hsp90 was observed in the presence of the modified peptide. This study provides an alternative approach and a lead peptide molecule for the rational design of effective inhibitors of Hsp90 function.